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Pharmacokinetic interaction between diltiazem and nortriptyline


Objective: Case report of a pharmacokinetic interaction between diltiazem and nortriptyline.

Methods: Determination of plasma nortriptyline concentrations by HPLC. Calculation of nortriptyline clearances and half-life by formulae used routinely in therapeutic drug monitoring.

Results: The average plasma concentration of nortriptyline at steady state (Css) divided by the amount of nortriptyline administered per time rose significantly in a patient with concomitant administration of diltiazem, suggesting increased bioavailability and/or decreased clearance of nortriptyline.

Conclusions: There is a significant pharmacokinetic interaction between diltiazem and nortriptyline, which is probably due to a reduction in the first pass clearance of nortriptyline, leading to an increase in its bioavailability.

Interactions with tricyclic antidepressants may be clinically important owing to the narrow therapeutic range and potential toxicity of these drugs. We have observed an interaction between diltiazem and nortriptyline, leading to increased plasma nortriptyline concentrations.

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Correspondence to S. Krähenbühl.

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Krähenbühl, S., Smith-Gamble, V. & Hoppel, C.L. Pharmacokinetic interaction between diltiazem and nortriptyline. Eur J Clin Pharmacol 49, 417–419 (1996).

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  • Toxicity
  • HPLC
  • Tricyclic
  • Diltiazem
  • Therapeutic Drug